Ryanodine receptor activation by Ca v 1.2 is involved in dendritic cell major histocompatibility complex class II surface expression.
Dendritic cells express the skeletal muscle ryanodine receptor (RyR1), yet little is known concerning its physiological role and activation mechanism. Here we show that dendritic cells also express the Ca(v)1.2 subunit of the L-type Ca(2+) channel and that release of intracellular Ca(2+) via RyR1 depends on the presence of extracellular Ca(2+) and is sensitive to ryanodine and nifedipine. Interestingly, RyR1 activation causes a very rapid increase in expression of major histocompatibility complex II molecules on the surface of dendritic cells, an effect that is also observed upon incubation of mouse BM12 dendritic cells with transgenic T cells whose T cell receptor is specific for the I-A(bm12) protein. Based on the present results, we suggest that activation of the RyR1 signaling cascade may be important in the early stages of infection, providing the immune system with a rapid mechanism to initiate an early response, facilitating the presentation of antigens to T cells by dendritic cells before their full maturation.
Vukcevic
Mirko
M
Department of Anaesthesia, Basel University Hospital, 4031 Basel, Switzerland.
Spagnoli
Giulio C
GC
Iezzi
Giandomenica
G
Zorzato
Francesco
F
Treves
Susan
S
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000737:chemistry*; D003713:Dendritic Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D002118:Calcium; D020746:Calcium Channels, L-Type; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D019837:Ryanodine Receptor Calcium Release Channel; D000097802:CD83 Antigen; C514350:CACNA1C protein, mouse; C419385:L-type calcium channel alpha(1C)